Protective Effect of Quercetin on Renal Tubular Cells and the Involvement with the Renin-Angiotensin-Aldosterone Axis

Abstract

Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid HIGHLIGHTS  Ischemia-reperfusion triggers acute kidney injury due to reactive oxygen species. Quercetin is an antioxidant flavonoid that modulate the Rennin-Angiotensin System. Quercetin prevents tubular cell death, oxidation, and mitochondrial depolarization. Quercetin interacts with the angiotensin AT1 receptor.2 Canuto, J.A.; et al.

Quercetin prophylaxis protects the kidneys by modulating the renin–angiotensin–aldosterone axis under acute hypobaric hypoxic stress

“…A study evaluating nephroprotective activity of quercetin against I/R and inhibition of RAAS pathway, performed a comparison between Lisinopril, losartan and quercetin and found that Lisinopril was a potent ACE inhibitor however, does not present protective effects against I/R-induced Acute Kidney Injury. Whereas, Losartan which is an important AT1-R blocker (ARB), exhibited moderate effects in comparison with quercetin 46 . Moreover, AT-1 inhibition results in surplus ACE that leads to the activation of Angiotensin-(1-7) pathway mediated by ACE2 imparting anti-inflammatory and antioxidant effects 47 .…”

The Effects of Quercetin on Apoptosis and Antioxidant Activity in a Renal Ischemia/Reperfusion Injury Animal Model

“…In general, reperfusion leads to ROS production and oxidative stress since oxygen is the last electron acceptor on the cellular respiratory chain. In addition, Quercetin is able to prevent oxidative damage in tubular renal cells after ischemic events, which seems to be linked to the ability to protect mitochondria from depolarization, which results in preventing cell death [64]. The major enzymes responsible for defense mechanisms against oxidative stress are superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).…”